The analysis of the HBV genome revealed the existence of 10 genotypes, named A-J. Evidence of the influence of the different genotypes in the natural history and treatment response to nucleoside/nucleotide analogues or interferon-based regimens is scant. HBV genotype F is one of the most prevalent circulating genotypes in South America and the Arctic Circle. Since most of the available information on HBV is from Asia, the US and Europe, it reflects their predominant genotypes: A, B, C and D. To date, the evidence is not fully confirmed, but it appears that genotype F chronic hepatitis B is associated with a more aggressive course of liver disease, reflected by higher histological indexes, a higher risk of development of hepatocellular carcinoma and a higher rate of liver-related mortality. In terms of treatment response, the available data is, unfortunately, even more limited; however, what data is available suggests acceptable and similar response rates to pegylated interferon-α2a in genotype F compared to genotype A. Response rates to nucleoside/nucleotide analogues is not influenced by genotype. The review of this limited data sheds light on the necessity to conduct further studies in South America and the Arctic Circle in order to better understand the different aspects of HBV genotype F, especially in relation to treatment response.